The small soil nematode, Caenorhabditis elegans, has become an excellent model for genetic analysis of the nervous system. The proposed research involves studies on the metabolism of the neurotransmitter acetylcholine in this nematode. Previous work by the Principal Investigator has identified a complex gene, cha-1, which is the structural gene for the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The goals of the current proposal are: 1) to use biochemical, genetic, and developmental analysis to examine the structure, function, and regulation of the gene complex and the enzyme, and 2) to elucidate the mechanisms by which genetic alterations in neurotransmitter levels lead to abnormal behavior and development. Much of the effort will be directed at testing a specific model of ChAT structure and function. These experiments will include the isolation of lethal and temperature- sensitive mutations in the cha-1 gene complex, fine-structure mapping of these and other mutations to determine the organization of the different subloci within the gene complex, and behavioral and developmental studies of these mutants. It is hoped that these studies will lead to an understanding of the role played by one factor in neural development and function. Although this research is of a basic nature, its relevance to health lies mainly in two areas. First alterations in acetylcholine metabolism and/or cholinergic function have been identified in many neurological and psychiatric disorders, including Alzheimer's disease, Huntington's disease, ALS and depression. Second, parasitic nematodes are a major world-wide health problem, and are often controlled by drugs and chemicals which effect or disrupt neural function. Better knowledge of the function and development of the nematode nervous system might aid in drug design and the treatment of parasitic nematodes.